PUBLICATION

Lead induced genotoxicity and hepatotoxicity in zebrafish (Danio rerio) at environmentally relevant concentration: Nrf2-Keap1 regulated stress response and expression of biomarker genes

Authors
Dey, K.K., Kamila, S., Das, T., Chattopadhyay, A.
ID
ZDB-PUB-240225-9
Date
2024
Source
Environmental Toxicology and Pharmacology   107: 104396 (Journal)
Registered Authors
Keywords
Hepatotoxicity, Hsp70, Lead (Pb), Nrf2-Keap1 pathway, Oxidative stress, Zebrafish
MeSH Terms
  • Animals
  • Biomarkers/metabolism
  • Chemical and Drug Induced Liver Injury*/genetics
  • DNA Damage
  • Kelch-Like ECH-Associated Protein 1/genetics
  • Kelch-Like ECH-Associated Protein 1/metabolism
  • Lead
  • NF-E2-Related Factor 2/genetics
  • NF-E2-Related Factor 2/metabolism
  • Oxidative Stress
  • Reactive Oxygen Species/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
PubMed
38395243 Full text @ Environ. Toxicol. Pharmacol.
Abstract
Genotoxic and hepatotoxic potentials of Pb at an environmentally relevant concentration (5 ppm) in zebrafish were investigated in the present study. Erythrocytic nuclear abnormality tests revealed the increased frequencies of abnormal erythrocytes after Pb exposure, indicating a strong genotoxic potential of Pb. Multiple stress-related parameters were further evaluated in liver, the major detoxifying organ. Pb caused increased production of ROS, which in turn caused severe oxidative stress. As a result, lipid peroxidation was increased, whereas reduced glutathione level and catalase activity was decreased. Alterations in liver histoarchitecture also served as evidence of Pb-induced hepatotoxicity. Pb-induced ROS stress triggered upregulation of Nrf2, Nqo1, Ho1; downregulation of Keap1, and altered mRNA expressions of Mn-sod, Cu/Zn-sod, gpx1, cyp1a, ucp2 suggesting involvement of Nrf2-Keap1-ARE signaling in cellular defence. Nrf2-keap1 is a sensitive biomarker of Pb-induced ROS stress. Overexpression of Hsp70 and other genes in hepatocytes might help cell survival under oxidative stress generation.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping